The proposed work involves two separate categories of compounds-diagnostic agents and weak analgesics: 1) To examine the role of plasma protein binding of cholegraphic agents in the isolated perfused rat liver to determine to what extent biliary excretion depends on the concentrations of free and protein-bound compounds. 2) To evaluate inhibition of organic acid uptake as an index of nephrotoxicity. Our work on weak analgesics is an outgrowth of our previous studies on the renal response to acute diuresis during the course of intravenous pyelography. We propose to continue our studies on the renal excretion of trace metabolites of phenacetin and acetaminophen and to determine their intra-renal distribution. Particular attention will be given to an attempt to identify N-hydroxyacetaminophen in biological fluids, especially urine.